Jack W. Tsao, M.D., D.Phil.

Funded in December, 2007: $200000 for 3 years

Using Imaging to Understand how the Brain Responds to Mirror Therapy for Phantom Limb Pain

The investigators will use conventional brain fMRI imaging in servicemen and women who undergo mirror therapy to reduce phantom limb pain from their amputated leg, to determine how this therapy reduces the pain and remodels cortical organization in the brain.

Following limb amputation, most patients continue to experience the presence of the missing limb, a sense of being able to move it, and pain emanating from it (phantom limb pain). The investigators recently demonstrated that phantom limb pain can be reduced by having the patient look at a mirror that reflects back to them the image of their intact foot, while they try to move their amputated foot. This therapy was more effective than either using a covered mirror or asking the patient to mentally visualize moving their phantom foot.

A few studies have found a relationship between phantom limb pain severity and degree of reorganization within the motor and sensory cortex in people with arm and hand amputations. Do similar changes occur in people with severe phantom pain from an amputated leg or foot and, if so, where are the new brain cell connections formed in response? The investigators hypothesize that direct input form the visual cortex modulates phantom limb pain by reducing cortical reorganization.

The investigators will use fMRI imaging to study how visual input during the course of mirror therapy can modulate pain severity and how pain reduction relates to cortical reorganization. First, they will use fMRI in 42 patients to visualize brain activation while they perform simple visual and motor tasks in order to learn how body maps in the motor and sensory areas of the brain change following leg amputation and to determine the association, if any, between brain reorganization and phantom limb pain. Then, they will monitor changes in brain activation patterns in the sensory and motor areas while patients undergo four weeks of mirror therapy. They will assess how visual input modifies (reduces) phantom limb pain through reorganization of sensory and motor brain areas, and determine whether pain reduction is associated with reduced reorganization within these brain areas.

Significance: The studies are anticipated to produce better understanding of the physiological interactions between phantom limb pain, visual input, and cortical reorganization, and lead to objective measures of treatment effectiveness and potentially to development of new, more effective, therapies to reduce the pain.

Following limb amputation, up to 98% of patients develop phantom limb pain (PLP), which is defined as the experience of sensations such as pain, itching, burning, or tingling in the amputated limb or the sensation that the limb is fixed in an uncomfortable position. Experimental evidence demonstrates that cortical maps representing a limb within the motor and somatosensory cortices reorganize following limb amputation. Previous studies have shown a correlation between the amount of cortical reorganization in upper extremity amputees and the severity of PLP.

Our group has recently demonstrated that the use of “mirror therapy” (viewing the reflected image of the intact limb while moving the amputated, or “phantom,” limb) can relieve PLP in lower extremity amputees, but the physiological basis for this effect remains unknown. We propose experiments which will use functional magnetic resonance imaging (fMRI) to examine how cortical maps in the brain change and determine the association between cortical remodeling and PLP after unilateral lower limb amputation and to assess why visual input is able to modulate PLP and how this affects cortical reorganization. Once completed, these studies will not only enable us to better understand the physiological basis of the interaction of the visual system, cortical reorganization, and the development of PLP but will also contribute to the development of a functional measure of the response of PLP to treatment and may result in the development of additional treatments for PLP.

Jack W. Tsao, M.D., D.Phil.

Dr. Tsao received his undergraduate and medical degrees from Harvard and doctorate from the University of Oxford, England. He completed neurology residency at the University of California-San Francisco and behavioral neurology fellowship at the University of Florida. He is currently Associate Professor of Neurology at the Uniformed Services University of the Health Sciences and is actively involved in medical student and resident education, clinical and basic science research, and telemedicine development. His clinical research is focused on treatments for phantom limb pain in amputees and methods for detecting and preventing traumatic brain injury and has a basic science research program studying axonal and synaptic degeneration.